PB1865: SINGLE-COUNTRY, MULTICENTER, RETROSPECTIVE, OBSERVATIONAL, DESCRIPTIVE COHORT STUDY OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS TREATED WITH VENETOCLAX IN ARGENTINA (VENARG).
Authors: C. Pagano Vilar, M. A. Pavlovsky, R. K. Tannuri, A. Enrico Mattos, M. Zerga, L. Guanchiale, R. Custidiano, A. Miroli, M. Higashigata, F. Figueroa, J. Pose Cabarcos, J. Real, L. Giordano, M. Miodosky, G. De Stefano, A. Federico, E. Klimovsky, M. S. Cugliari
Journal: HemaSphere (2022)

Background: Venetoclax (VEN), an oral BCL-2 inhibitor, has shown efficacy and good tolerability in pivotal clinical trials for patients (pt) with Chronic Lymphocytic Leukemia (CLL). However, real world data is limited and no local nor regional information from Argentina has been reported. Aims: To describe the epidemiological characteristics, effectiveness of therapy, and safety and accessibility outcomes in CLL pt treated with VEN in the real-world setting in Argentina. Methods: Study including pt ≥18 years old with CLL according to the iwCLL criteria treated with VEN as per label, in monotherapy or in combination to Anti CD20 prior to 31 March 2021. Descriptive statistics and Kaplan Meier curves were utilized, using the Statistical Package for Social Sciences (SPSS). Results: Fifty seven CLL pt treated with VEN from 13 sites were included, with a median age of 58 years (38-80) at diagnosis; 35% were female. At baseline, 94.5% (52/55) were ECOG 0-1, 43.8% (25/57) intermediate and 33.3% (19/57) high RAI stage. From 46 pt tested, 24 were found to have deletion 17 and 15/46 deletion 11q. Comorbidities were experienced by 38pt (66.7%) being high blood pressure the most frequently reported (32pt, 56.1%) and CIRS score was >6 in 27pt (47.4%). Twenty one pt were at high risk of tumor lysis syndrome (TLS) (36.8%). VEN was received as monotherapy by 24pt (42.1%) and as first line therapy by 15pt (26.3%). In this cohort 94,7% had health insurance coverage. As to accessibility, 11pt (19.3%) were supplied with drug after >2 months, including 10/54 covered with health insurance. Statistically significant differences were observed in access to the drug according to coverage (p:0.015). With a median follow up of 18,3 months (4-39) ORR was 91.2% (CR 24.6% and PR 66.7%) as per iwCLL criteria (32/38 pt were not performed a bone-marrow procedure for response assessment). No statistically differences were observed in terms of response rates between pt with VEN monotherapy vs VEN plus Anti CD20 (Chi2:2,737; p:0.434) either pt treated in first line vs subsequent line (Chi2:1.948; p:0.583). Progression-free survival (PFS) reported was 91.2%, with 5pt presenting disease progression. Estimated PFS at 24 months was 90.8% (95% CI 82.0%-99.6%) (Figure). Overall survival (OS) was 89.5%, with 6 deaths (2 due to CLL progression) and estimated OS at 24 months was 90.5% (95% CI 81.0%-99.9%). Related to VEN safety profile, 4 drug-related serious adverse events were observed (hospitalizations due to infections, pneumonia, perianal abscess, disseminated herpes zoster). Twenty grade 3 CTCAE (15pt) were reported, being leukopenia and neutropenia the most common. TLS was reported in 2pt (1 high-risk pt with clinical and laboratory lysis/1 low-risk pt only lab tests). None of them result in therapy discontinuation. Mean duration of hospitalization during ramp-up was 5.4 days (range 1-11) in the 21pt with high risk of TLS and 4,8 days (range 0 – 16) for pt at intermediate risk (24p). Nine pt (15.8%) discontinued treatment (2 due to safety reasons/4 due to progression); 9pt temporarily discontinued treatment. Dose was reduced due to safety reasons in 11pt. Image:Summary/Conclusion: VENARG study included a cohort of unselected naïve and previously treated Argentinian CLL pt, receiving VEN in monotherapy or combination with Anti CD20. Despite the high percentage of pt with high cytogenetic risk and differences in drug access in this cohort, outcomes analyzed with the use of VEN in the real-world setting in Argentina suggest an effectiveness comparable to that reported in pivotal clinical trials and no unexpected adverse events.